• Lijie Han, Haiyan Zhang, Shan Chen, Lizhi Zhou, Yuanyuan Li, Ke Zhao, Fen Huang, Zhiping Fan, Li Xuan, Xin Zhang, Min Dai, Qianyun Lin, Zhongxing Jiang, Jie Peng, Hua Jin, and Qifa Liu.
• Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Hematology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
• Biol. Blood Marrow Transplant. 2019 Oct 1; 25 (10): 1944-1955.

AbstractThe intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD). However, whether intestinal microbiota can predict the development of aGVHD has been reported only rarely. Here we conducted a prospective study of microbiota in 141 patients after allogeneic hematopoietic stem cell transplantation. We found lower microbiota diversity in the aGVHD group compared with the non-aGVHD group at day 0 and day 15 ± 1 (P = .018 and .009, respectively). Diversity was negatively associated with conditioning intensity (P = .017, day 0; P = .045, day 15) and β-lactam antibiotic administration (P = .004, day 15). Intensified conditioning and β-lactam antibiotics were associated with a lower regulatory T (Treg)/T helper 17 (Th17) cell ratio at day 15 (P = .030 and .047, respectively). At day 15, the levels of the inflammatory factors (tumor necrosis factor α, interleukin [IL]-6, IL-17A, IL-1β, and lipopolysaccharide) were higher in the intensified conditioning group compared with the standard group (P < .05). The accumulated intestinal microbiota (AIM) score was defined as microbiota diversity and gradient of the 4 bacterials (Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, and Enterobacteriaceae) at day 15 post-transplantation. The AIM score was positively correlated with aGVHD grade (r = .481, P < .001), and the AIM score could be predictive of the development of aGVHD (grade II-IV aGVHD: area under the curve [AUC], .75, P < .001; grade III-IV aGVHD: AUC, .84, P < .001). These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment may predict the development of aGVHD.Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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